During the past 20 or so years, this project has been concerned largely with two naturally occurring slow viral diseases of animals, namely, scrapie of sheep and goats and Aleutian disease of mink. Emphasis has ben on the host-virus-interactions that result in the slow evolution of these diseases--polioencephalopathy in scrapie and progressive glomerulonephritis in Aleutian disease. Quantitative virologic information, obtained by endpoint titration in animal assay systems, and morphologic findings have been used to gain an insight into the pathogenesis of each disease. In scrapie, virus replicates for many months mainly in lymphoreticular tissues before reaching the central nervous system where secondary replication gives rise to fatal degenerative neurologic disease. In Aleutian disease, virus replicates early in lymphoreticular tissues, liver, kidney, and intestine. Depending on the strain of virus and genotype of mink, this soon leads to viremia. When it is sustained, virus in the blood forms soluble complexes with specific antibody that become deposited in glomeruli, giving rise to slowly progressive renal disease. Such information on both diseases has implications for understanding broadly comparable human diseases.